July 15, 2003 | Physicians treating Alzheimer's disease face a quandary: the best way to diagnose Alzheimer's is after the patient's death, when brain tissue can be examined under the microscope. But two key drugs approved to treat Alzheimer's -- Aricept (Pfizer) and Exelon (Novartis) -- are for early stages of the disease, when it's hard to distinguish it from the mental lapses associated with aging or depression.

A handheld could help on both fronts. With neurological testing software from U.K.-based Cambridge Cognition, a personal digital assistant (PDA) can diagnose Alzheimer's more accurately than low-tech paper tests -- and before doctors can see unambiguous clinical signs of the disease. The software can even distinguish patients with Alzheimer's from those with other conditions. “Having [the application] on a PDA is quite useful,” says Rupert McShane, a psychiatrist specializing in the elderly in Oxford, England. “I can carry it around in my pocket. I see patients at home and in different settings.”

Last month, Cambridge Cognition announced a 45-hospital network in Britain, Nuffield Hospitals Health Screening, would offer the first international deployment of a noninvasive, electronic test to diagnose Alzheimer's. "There are no PDA-based tests specific for Alzheimer's available in the U.S. or anywhere else in the world," says Ian Harris, commercial director of Cambridge Cognition. "This is the first."

The PDA uses a shape-based memory test that can continue to monitor the progression of Alzheimer's in its later stages, when tests based on language or factual knowledge ("Who is the President of France?") can become more problematic -- and embarrassing to the patient if no answer comes to mind.

The Nuffield hospitals will advertise the devices as a competitive advantage -- a technology that can attract retirees concerned about faltering memories without embarrassing them. Such patients are mostly the "worried well": anxious people in good health. But some with the earliest manifestations of Alzheimer's may benefit from new medicines. The PDA could be a quick, simple tool to help sort out who could genuinely benefit from new drugs.

Not surprisingly, companies like Pharmacia and Gemini Genomics are also working with Cambridge Cognition's test in clinical research. And Cambridge Cognition is in discussions with hospital groups and governmental agencies about commercializing the test in the U.S., where it is currently only available in research settings and on desktop computers with attached touchscreens.

The company, to be sure, is hardly a newcomer in testing for central nervous system disorders. Its suite of digital tests for mental functioning, called CANTAB, were originally developed at Cambridge University and have been licensed to 400 academic hospitals around the world -- and featured in 200 peer-reviewed scientific articles. The key CANTAB test for Alzheimer’s is the company's Paired Associates Learning (PAL) test, which involves no words at all.

Instead, patients must remember the location of a geometric shape. The PAL test gets harder as it goes along but remains simple enough to accommodate both normal patients and those with advanced dementia. Scientifically, a key selling point of PAL is that it is simple to administer. And a nurse or researcher who may have their own style of administering the test will not skew the results. "Paper and pencil tests require a higher degree of professional input at the front end," says Cambridge Cognition's Harris. In [England], one session of testing costs approximately $130 and is covered by insurance.

The PDA, the company says, does not need to be recalibrated as often as a larger computer touchscreen, and it can be easily delivered to bedridden patients, who can feel intimidated by a standard computer but not by a tiny handheld.

Competition for the device is paper-based. The two best-known tests are the Alzheimer's Disease Assessment Scale/Cognitive Subscale (known as ADAS-Cog in the U.S.) and the Mini-Mental State Examination (known as MMSE elsewhere in the world). "It's the inertia that's generated by the medical community not wishing to change," says Harris. "Change is unsettling. In the U.S. and the U.K. [there is growing awareness that] the A-Cog and MMSE are fairly gross measures of cognition that are not as sensitive to early detection of Alzheimer's as our test." One British study of the MMSE reported an 86-percent error rate in diagnosing patients with garden-variety dementia.

Cambridge Cognition, in contrast, can happily cite the Journal of the International Neuropsychological Society, where Kylie Fowler and her team at Austin Hospital in Victoria, Australia, found that PAL was able to identify Alzheimer's patients long before other well-accepted tests. In that study, Fowler followed people with memory troubles for two years. She calculated the PAL test could pick out 98 percent of the people destined for Alzheimer's years before doctors could.

The technical director at Cambridge Cognition, John Hammond, notes that the software was written in IBM's Java Virtual Machine to assure maximum portability. So the code will run on Palm devices as well as those from other manufacturers. The Nuffield hospital network had originally tested the software on a desktop and didn't need much persuading to take the system on a PDA. "It's a good indication of how acceptable a portable, high-tech gadgetry is in this environment," says Hammond.